The P.I. has previously demonstrated that a 36kDa Myelin Basic Protein Kinase (MBP Kinase) is activated during ceramide-induced apoptosis in HL60 promyelocytic leukemia cells. This kinase is activated in the subset of cells that have actually initiated apoptosis. Purification and microsequencing reveal that the kinase is derived from a previously identified Mammalian Sterile Twenty (MST) Kinase, two isoforms of which were cloned and characterized by the P.I.. The P.I. now plans to: 1) characterize the cellular regulation of MST kinases in response to stress/apoptotic signals; 2) characterize the physiological roles of these kinases using an inducible expression system and genetically engineered mutants and 3) characterize the signalling pathway that leads to activation of the MST kinases.